Biomaterial Database

Mechanism of misoprostol stabilization in hydroxypropyl methylcellulose. 1991

T T Kararli, and T Catalano, and T E Needham, and P M Finnegan

G. D. Searle & Co., Product Development, Skokie, IL 60077.

The stability of misoprostol oil is significantly improved in a hydroxypropyl methylcellulose (HPMC) dispersion (1:100). In order to understand the enhanced stability of misoprostol oil in HPMC, the physical state of misoprostol oil in HPMC films was investigated using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and transmission IR (TIR). Further, to determine the effect of polymer structure and the mobility of both water and misoprostol on misoprostol stability, the rate of misoprostol degradation was investigated in the misoprostol/HPMC dispersion (1:100) at 55 degrees C. The water sorption isotherm of the dispersion at 55 degrees C was determined, at seven different relative humidities, ranging from zero to 81%. The DSC and DMA measurements indicated that misoprostol oil, up to 29% in dry weight, is molecularly dispersed in the glassy HPMC. The TIR studies showed no evidence of complexation between misoprostol and HPMC. Stability studies of the misoprostol/HPMC (1:100) dispersion indicated that the first-order rate constants for misoprostol degradation increased in a concave-up fashion as the water content of the dispersion increased. Below two percent water content, the rate of misoprostol degradation was found to be minimal. Overall, it is suggested that misoprostol is stabilized in the dispersion by being molecularly dispersed in HPMC. Further, the glassy state of HPMC should reduce the mobility of misoprostol and water, leading to a minimal rate of degradation for misoprostol at low moisture levels.

UI	MeSH Term	Description	Entries
D008747	Methylcellulose	Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative.	BFL,Celevac,Cellothyl,Cellulone,Citrucel,Cologel,Dacryolarmes,Methocel,Methyl Cellulose,Muciplasma,Cellulose, Methyl
D002152	Calorimetry, Differential Scanning	Differential thermal analysis in which the sample compartment of the apparatus is a differential calorimeter, allowing an exact measure of the heat of transition independent of the specific heat, thermal conductivity, and other variables of the sample.	Differential Thermal Analysis, Calorimetric,Calorimetric Differential Thermal Analysis,Differential Scanning Calorimetry,Scanning Calorimetry, Differential
D002623	Chemistry Techniques, Analytical	Methodologies used for the isolation, identification, detection, and quantitation of chemical substances.	Analytical Chemistry Techniques,Analytical Chemistry Methods,Analytical Chemistry Method,Analytical Chemistry Technique,Chemistry Method, Analytical,Chemistry Methods, Analytical,Chemistry Technique, Analytical,Method, Analytical Chemistry,Methods, Analytical Chemistry,Technique, Analytical Chemistry,Techniques, Analytical Chemistry
D002627	Chemistry, Physical	The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes.	Physical Chemistry,Chemistries, Physical,Physical Chemistries
D004355	Drug Stability	The chemical and physical integrity of a pharmaceutical product.	Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D013055	Spectrophotometry, Infrared	Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	IR Spectra,Infrared Spectrophotometry,IR Spectras,Spectra, IR
D013816	Thermodynamics	A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)	Thermodynamic
D014867	Water	A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Hydrogen Oxide
D016595	Misoprostol	A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties.	Apo-Misoprostol,Cytotec,Glefos,Misoprostol, (11alpha,13E)-Isomer,Misoprostol, (11alpha,13E,16R)-Isomer,Misoprostol, (11alpha,13Z)-(+-)-Isomer,Misoprostol, (11alpha.13E,16S)-Isomer,Misoprostol, (11beta,13E)-(+-)-Isomer,Misoprostol, (11beta,13E,16R)-Isomer,Misoprostol, (11beta,13E,16S)-Isomer,Novo-Misoprostol,SC-29333,SC-30249,Apo Misoprostol,Novo Misoprostol,SC 29333,SC 30249,SC29333,SC30249
D055598	Chemical Phenomena	The composition, structure, conformation, and properties of atoms and molecules, and their reaction and interaction processes.	Chemical Concepts,Chemical Processes,Physical Chemistry Concepts,Physical Chemistry Processes,Physicochemical Concepts,Physicochemical Phenomena,Physicochemical Processes,Chemical Phenomenon,Chemical Process,Physical Chemistry Phenomena,Physical Chemistry Process,Physicochemical Phenomenon,Physicochemical Process,Chemical Concept,Chemistry Process, Physical,Chemistry Processes, Physical,Concept, Chemical,Concept, Physical Chemistry,Concept, Physicochemical,Concepts, Chemical,Concepts, Physical Chemistry,Concepts, Physicochemical,Phenomena, Chemical,Phenomena, Physical Chemistry,Phenomena, Physicochemical,Phenomenon, Chemical,Phenomenon, Physicochemical,Physical Chemistry Concept,Physicochemical Concept,Process, Chemical,Process, Physical Chemistry,Process, Physicochemical,Processes, Chemical,Processes, Physical Chemistry,Processes, Physicochemical